In her early years, Canals-Barrera worked extensively in theater in both Miami and Los Angeles. In 1992, she began starring on Telemundo Spanish-language telenovela Marielena. She later had the recurring role in the short-lived 1993 Fox comedy-drama series, Key West. During the 1990s, Canals-Barrera also guest starred in a number of television series, such as 21 Jump Street, Murder, She Wrote, Almost Perfect, and Caroline in the City. Her first regular role was on the short-lived NBC sitcom The Tony Danza Show in 1997.

In early 2000s, Canals-Barrera had supporting roles in films America’s Sweethearts, The Master of Disguise and Imagining Argentina. She has gained much recognition with comic book fans in recent years for her role as Hawkgirl/Shayera Hol on Bruce Timm’s Justice League (2001–04) and Justice League Unlimited (2005–06) series. She also had a recurring role in Static Shock as Shelly Sandoval, a news reporter, and in Danny Phantom as Danny Fenton/Phantom’s high school crush, Paulina. She also performed the voice of Mercedes “Meche” Colomar in the 1998 video game Grim Fandango. Canals-Barrera also played incidental characters in two episodes on the TV series The Boondocks (“Grandad’s Fight” and “Home Alone”).

From 2007 to 2012, Canals-Barrera co-starred as Theresa Russo, the mother of lead character Alex Russo (Selena Gomez), in the Disney Channel family sitcom Wizards of Waverly Place. She also co-starred in Wizards of Waverly Place: The Movie, a 2009 Disney Channel Original movie based on series. Canals-Barrera also appeared in the Disney Channel Original Movies Camp Rock (2008) and Camp Rock 2: The Final Jam (2010), alongside Demi Lovato in the role of her mother, Connie Torres. In 2011 she appeared opposite Tom Hanks and Julia Roberts in the romantic comedy film Larry Crowne.

In 2014, Canals-Barrera was cast as Hilda, the house manager of the country club where most of the action takes place, in the ABC soapy comedy-drama series Members Only created by Susannah Grant. However, it got cancelled by the network before its premiere. Later in that year she joined the cast of ABC comedy series Cristela, as Cristela Alonzo’s character sister.

On August 27, 2018, it was revealed by TVLine that Canals-Barrera was cast as the mother of Fernando Hernandez-Guerrero-Fernandez-Guerrero on the Netflix series Fuller House.